1.Serum levels of interleukin-38 and interleukin-1β in the acute phase of Kawasaki disease in children.
Xin-Yan ZHANG ; Ting HE ; Jia-Yun LING ; Xiu-Fen HU ; Yu WEN ; Jun WEI ; Hui-Ling LU
Chinese Journal of Contemporary Pediatrics 2018;20(7):543-548
OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).
METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).
RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).
CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.
Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood
2.Prognostic significance of plasma gelsolin in severe burn patients with sepsis.
Lifeng HUANG ; Yongming YAO ; Ning DONG ; Lixin HE ; Qinghong ZHANG ; Yan YU ; Zhiyong SHENG
Chinese Journal of Burns 2016;32(2):77-81
OBJECTIVETo investigate the changes in plasma gelsolin (pGSN) levels in severe burn patients with sepsis, and to evaluate the prognosis of patients when combined with other related clinical indexes.
METHODSSixty-five severe burn patients with sepsis hospitalized from June 2013 to June 2015 conforming to the study criteria were divided into death group (n=24) and survival group (n=41) according to the clinical outcome on post sepsis diagnosis day (PSD) 28. The pGSN levels of patients were determined on PSD 1, 3, 7, and 14 with double antibody sandwich enzyme-linked immunosorbent assay. The serum level of C-reactive protein (CRP), serum level of procalcitonin, lactate level of arterial blood, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were determined or recorded on PSD 1. Data were processed with repeated measurement analysis of variance, t test, and chi-square test. On PSD 1, the pGSN level, serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of 65 patients were collected to screen the independent risk factors related to death with single factor and multi-factor Logistic regression analysis. Receiver operating characteristic (ROC) curves of the independent risk factors related to death were plotted to evaluate the predictive power for death in 65 patients.
RESULTS(1) The pGSN levels of patients in death group on PSD 1, 3, 7, and 14 were respectively (146±44), (85±24), (28±7), and (19±4) mg/L, obviously lower than those in survival group [(287±82), (179±51), (196±56), and (249±67) mg/L, with t values from 1.735 to 4.304, P<0.05 or P<0.01]. (2) The serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of patients in death group on PSD 1 were respectively (56±7) mg/L, (12.54±0.82) μg/L, (2.74±0.27) mmol/L, (24.3±2.4) points, and (11.43±0.57) points, significantly higher than those in survival group [(35±4) mg/L, (2.38±0.16) μg/L, (1.83±0.12) mmol/L, (15.0±1.5) points, and (7.22±0.23) points, with t values from 1.902 to 3.883, P<0.05 or P<0.01]. (3) Multi-factor Logistic regression analysis showed that the pGSN level (odds ratio: 6.83, 95% confidence interval: 4.33-10.25, P<0.01) and APACHE II score (odds ratio: 5.27, 95% confidence interval: 2.28-9.16, P<0.01) were the independent risk factors related to death in 65 patients on PSD 1. (4) The total areas under the ROC curves of pGSN level and APACHE II score for predicting death of 65 patients on PSD 1 were respectively 0.89 and 0.86, and 142 mg/L and 21 points were respectively chosen as the optimal threshold values, with sensitivity of 87% and 83% and specificity of 86% and 89%.
CONCLUSIONSFor severe burn patients with sepsis, lowering of pGSN level and elevation of APACHE II score are obviously correlated with increase in case fatality rates. Monitoring the dynamic changes in pGSN level and APACHE II score during the early stage may be useful to predict the prognosis of severe burn patients with sepsis.
Burns ; complications ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enzyme-Linked Immunosorbent Assay ; Gelsolin ; blood ; Hospitalization ; Humans ; Organ Dysfunction Scores ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Regression Analysis ; Risk Factors ; Sepsis ; blood ; diagnosis ; Severity of Illness Index
3.Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection.
Yonsei Medical Journal 2016;57(5):1139-1144
PURPOSE: Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. MATERIALS AND METHODS: Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. RESULTS: Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798-0.917, p<0.001], 0.808 (95% CI, 0.738-0.878, p<0.001), and 0.638 (95% CI, 0.544-0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). CONCLUSION: Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections.
Area Under Curve
;
Arthritis, Gouty/*diagnosis
;
Bacterial Infections/*diagnosis
;
Biomarkers/blood
;
Blood Sedimentation
;
C-Reactive Protein/metabolism
;
Calcitonin/*blood
;
Case-Control Studies
;
Cross-Sectional Studies
;
Diagnosis, Differential
;
Female
;
Humans
;
Inflammation
;
Leukocyte Count
;
Male
;
Middle Aged
;
Protein Precursors/*blood
;
Sensitivity and Specificity
;
Uric Acid/blood
4.Effects of early oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury.
Kedai SUN ; Zhiwei DONG ; Jing CHEN ; Pan LIU ; Yali GONG ; Yizhi PENG
Chinese Journal of Burns 2015;31(1):25-29
OBJECTIVETo explore the effects of oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury at early stage.
METHODSTwenty-four patients with severe burn injury admitted to our burn ward from August 2013 to September 2014, conforming to the study criteria, were divided into conventional therapy group (n = 12) and early enteral feeding group (n = 12) according to the random number table. Patients in conventional therapy group received conventional treatment immediately after admission, while those in early enteral feeding group were orally given 100 mL of a mixture of glutamine, probiotics, and prebiotics once a day besides conventional treatment for 7 days. Serum levels of diamine oxidase (DAO) and procalcitonin (PCT) and plasma level of LPS were determined by ELISA before treatment and on treatment day (TD) 1, 3, 7, 14, and 21. Wound secretion and blood samples were collected for bacterial culture within the 21 TD. The incidence of MODS within the 21 TD was observed. Data were processed with Fisher's exact test, rank sum test, analysis of variance for repeated measurement, and LSD-t test.
RESULTS(1) Serum levels of DAO in patients of early enteral feeding group on TD 7, 14, and 21 were respectively (14.9 ± 3.7), (12.4 ± 3.1), and (9.5 ± 0.7) ng/mL, which were significantly lower than those of conventional therapy group [(17.5 ± 4.0), (16.3 ± 3.3), and (13.0 ± 1.1) ng/mL, with t values from 2.913 to 15.304, P values below 0.01]. Serum levels of DAO at the other time points were close between the two groups (with t values from -0.598 to 0.139, P values above 0.05). (2) Compared with serum levels of PCT in patients of conventional therapy group [(11.7 ± 20.9) and (12.9 ± 23.9) ng/mL], those of early enteral feeding group were significantly lower on TD 7 and 14 [(2.7 ± 8.1) and (2.0 ± 5.6) ng/mL, with Z values respectively -2.919 and -2.139, P < 0.05 or P < 0.01]. Serum levels of PCT at the other time points were close between the two groups (with Z values from -1.833 to -0.346, P values above 0.05). (3) Plasma level of LPS in patients of early enteral feeding group on TD 7 was (33 ± 56) pg/mL, which was significantly lower than that of conventional therapy group [(102 ± 108) pg/mL, Z = -2.046, P < 0.05]. Plasma levels of LPS at the other time points between the two groups showed no significant difference (with Z values from -2.003~-0.526, P values above 0.05). (4) Positive results in bacterial culture of wound secretion were approximately the same between the two groups (P > 0.05). Bacterial culture of blood was positive in 7 patients of conventional therapy group and 1 patient of early enteral feeding group, showing significantly statistical difference (P < 0.05). MODS was observed in 1 patient of conventional therapy group, showing no significantly statistical difference with that of early enteral feeding group (no patient, P > 0.05).
CONCLUSIONSEarly intestinal feeding of mixed enteral nutritional agent in addition to conventional therapy can effectively promote repair of the impairment of intestinal mucosal barrier, protect integrity of intestinal mucosa, reduce damage to intestines, and alleviate inflammatory response in patients suffering from severe burn injury.
Administration, Oral ; Amine Oxidase (Copper-Containing) ; blood ; Burns ; metabolism ; therapy ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Protein Precursors ; blood ; Treatment Outcome ; Wound Healing
5.Clinical study on application of intermittent hemofiltration combined with hemoperfusion in the early stage of severe burn in the prevention and treatment of sepsis.
Wanli GUO ; Jin LEI ; Email: LEIJINLD@163.COM. ; Peng DUAN ; Xiaoming MA
Chinese Journal of Burns 2015;31(4):248-253
OBJECTIVETo investigate the effects of application of intermittent hemofiltration combined with hemoperfusion (HP) in the early stage of severe burn in the prevention and treatment of sepsis.
METHODSForty severely burned patients, admitted to our burn ward from June 2011 to March 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and blood purification group (BP, n=20) according to the random number table. Patients in group CT received CT according to the accepted principles of treatment for a severe burn. Patients in group BP received CT and intermittent hemofiltration combined with HP once respectively on post injury day (PID) 3, 5, and 7, spanning 6 to 8 hours for each treatment. On PID 3, 5, 7, 10, and 14, body temperature, heart rate, and respiratory rate were recorded; white blood cell count (WBC), neutrophil granulocytes, blood urea nitrogen (BUN), and creatinine were determined; levels of IL-1, IL-6, TNF-α, and high-mobility group box 1 (HMGB1) in serum were determined by ELISA; level of LPS in serum was determined with the chromogenic substrate limulus amebocyte lysate method; level of procalcitonin (PCT) in serum was determined by double antibody sandwich immune chemiluminescence method. The symptoms and signs of sepsis were observed during the treatment. Data were processed with Fisher's exact test, chi-square test, analysis of variance for repeated measurement, and LSD-t test.
RESULTS(1) Except for that on PID 5, the mean body temperature of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.87 to 2.97, P values below 0.05). The heart rate was significantly slower in patients of group BP than in group CT from PID 3 to 14 (with t values from 1.78 to 3.59, P values below 0.05). Except for that on PID 3, the respiratory rate of patients in group BP was significantly slower than that of group CT at each of the rest time points (with t values from 1.93 to 2.85, P values below 0.05). (2) The levels of WBC, neutrophil granulocytes, BUN, and creatinine of patients in group BP were significantly lower than those of group CT (with t values from 1.78 to 4.23, P values below 0.05). (3) Except for that on PID 3, the level of IL-1 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.97 to 4.16, P values below 0.05). Except for that on PID 7, the level of IL-6 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 2.11 to 6.34, P values below 0.05). The levels of TNF-α and HMGB1 of patients in group BP were significantly lower than those of group CT from PID 3 to 14 (with t values from 1.98 to 5.29, P values below 0.05). (4) On PID 3, 5, 7, 10, and 14, the levels of LPS and PCT of patients in group BP were respectively (0.23 ± 0.07), (0.27 ± 0.09), (0.22 ± 0.06), (0.20 ± 0.08), (0.15 ± 0.07) EU/mL, and (0.44 ± 0.12), (0.67 ± 0.13), (0.74 ± 0.13), (0.64 ± 0.12), (0.71 ± 0.10) ng/mL, and they were lower than those of group CT [(0.37 ± 0.08), (0.45 ± 0.09), (0.56 ± 0.09), (0.48 ± 0.08), (0.40 ± 0.08) EU/mL, and (0.74 ± 0.11), (1.16 ± 0.12), (1.40 ± 0.13), (1.55 ± 0.15), (1.49 ± 0.14) ng/mL, with t values from 1.88 to 3.43, P values below 0.05]. (5) The incidence of sepsis of patients in group BP was obviously lower than that of group CT (χ² = 6.94, P<0.01).
CONCLUSIONSIntermittent hemofiltration combined with HP can effectively improve blood biochemical indexes and vital signs and reduce the occurrence of burn sepsis by decreasing the levels of proinflammatory cytokines, LPS, and PCT.
Biomarkers ; blood ; Burns ; blood ; complications ; immunology ; therapy ; Calcitonin ; Calcitonin Gene-Related Peptide ; Cytokines ; blood ; HMGB1 Protein ; Hemofiltration ; methods ; Hemoperfusion ; methods ; Humans ; Interleukin-1 ; blood ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Protein Precursors ; Sepsis ; blood ; immunology ; prevention & control ; therapy ; Serum ; Severity of Illness Index ; Treatment Outcome ; Tumor Necrosis Factor-alpha
6.Cutoff value of serum procalcitonin as a diagnostic biomarker of infection in end-stage renal disease patients.
Wan Soo LEE ; Dae Woong KANG ; Jong Hun BACK ; Hyun Lee KIM ; Jong Hoon CHUNG ; Byung Chul SHIN
The Korean Journal of Internal Medicine 2015;30(2):198-204
BACKGROUND/AIMS: Serum procalcitonin (PCT) levels are low in healthy individuals but are elevated in patients with a serious bacterial infection or sepsis. In this study, we examined the ability of serum PCT concentration to diagnose infections in end-stage renal disease (ESRD) patients, and sought to determine an appropriate threshold level. METHODS: Serum PCT levels were measured in ESRD patients on antibiotic therapy for a suspected bacterial infection (ESRD infection [iESRD] group, n = 21), and compared with those of ESRD patients on hemodialysis with no sign of infection (ESRD control [cESRD] group, n = 20). RESULTS: The mean serum PCT concentration of the iESRD group was significantly higher than in the cESRD group (2.95 +/- 3.67 ng/mL vs. 0.50 +/- 0.49 ng/mL, p = 0.006), but serum PCT concentrations did not correlate with severity of infection. The optimized threshold level derived for serum PCT was 0.75 ng/mL, rather than the currently used 0.5 ng/mL; this threshold demonstrated a sensitivity and specificity of 76.2% and 80.0% for infection and 100% and 60.6% for systemic inflammatory response syndrome, respectively, compared with the cutoff of 0.5 ng/mL. CONCLUSIONS: This study suggests that serum PCT at a cutoff value of 0.75 ng/mL is an appropriate indicator of infection in ESRD patients.
Adult
;
Aged
;
Area Under Curve
;
Bacterial Infections/*blood/complications/*diagnosis/microbiology
;
Biomarkers/blood
;
Calcitonin/*blood
;
Case-Control Studies
;
Female
;
Humans
;
Inflammation Mediators/*blood
;
Kidney Failure, Chronic/*complications/diagnosis/therapy
;
Male
;
Middle Aged
;
Peritoneal Dialysis
;
Predictive Value of Tests
;
Protein Precursors/*blood
;
ROC Curve
;
Renal Dialysis
;
Reproducibility of Results
;
Up-Regulation
7.Protection and Mechanism of Qingyuan Shenghua Decoction on Multiple Organs of Sepsis Patients after Bone Trauma.
Feng-ying WANG ; Tie-zhu YANG ; Song-lin MING ; Li-li YOU ; Li-hui XU ; He LI ; Qing-feng SONG ; Liang-ye LI
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(7):778-782
OBJECTIVETo observe the protection of Qingyuan Shenghua Decoction (QSD) on multiple organs of sepsis patients after bone trauma, and to preliminarily explore its mechanism.
METHODSTotally 60 sepsis patients after bone trauma were randomly assigned to the treatment group and the control group according to random digit table, 30 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took QSD or were nasally fed with QSD, one dose per day for 1 week. Changes of WBC, oxygenation index (PaO2/FiO2), serum creatinine (SCr), total bilirubin (TBIL), aspartate aminotransferase (AST), fibrinogen (FIB), D-dimer (DD), activated partial thromboplastin time (APTT), pro-calcitonin (PCT), C-reactive protein (CRP), heart rate (HR), mean arterial pressure (MAP), intra-abdominal pressure, scores for Acute Physiology and Chronic Health Evaluation II (APACHE II), sequential organ failure assessment (SOFA) scores were observed before treatment and on day 1, 3 and 7 after treatment.
RESULTSCompared with the control group at the same time point, MAP increased at post-treatment day 1 and 3; CRP, APTT, HR, SCr, TBIL, AST, intra-abdominal pressure at post-treatment day 3 obviously decreased in the treatment group (P < 0.05, P < 0.01). WBC, SOFA scores, PCT, CRP, APACHE II, APTT, D-D, HR, SCr, TBIL, AST and intra-abdominal pressure significantly decreased; FIB, MAP and PaO2/FiO2 obviously increased at post-treatment day 7 (P < 0.05, P < 0.01).
CONCLUSIONQSD had good protective effect on multiple organ function in sepsis patients after bone trauma, and its mechanism might be related with effectively clearing endotoxin, alleviating inflammatory reactions, and fighting against coagulation dysfunction.
APACHE ; Blood Coagulation ; Bone Diseases ; complications ; C-Reactive Protein ; metabolism ; Calcitonin ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Inflammation ; Partial Thromboplastin Time ; Protein Precursors ; metabolism ; Sepsis ; drug therapy ; etiology
8.Clinical significance of PCT, CRP, ESR, WBC count as predictors in postoperative early infectious complications with fever after posterior lumbar internal fixation.
Le WANG ; Bo YANG ; Biao YIN ; Zhi ZHANG ; Liang ZHANG ; Long TANG ; Ai-ju LOU
China Journal of Orthopaedics and Traumatology 2015;28(1):66-70
OBJECTIVETo evaluate the role of serum level of procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) as predictors in postoperative early infectious complications with fever after posterior lumbar internal fixation (PLIF).
METHODSA retrospective study was conducted from January 2012 to January 2014. Fifty-two patients with fever in the early stage(within 10 days) after the PLIF were collected in the study. They were divided into infection group and non-infection group (group A and group B) according to the results of postoperative blood culture. There were 26 patients in group A and 32 patients in group B. The values of PCT, CRP, ESR, and WBC count were compared and analyzed between two groups.
RESULTSThe values of PCT, CRP, and ESR in group A were higher than those of group B. Meanwhile, CRP and ESR in group B were still higher than the normal range. Among the 26 patients with infections (group A), PCT was superior to CRP and ESR, had a good ability in discriminating different kinds of postoperative infections. The area under the ROC curve of serum PCT levels was the largest (CI 95% was 0.81 to 0.98) in the indexs; and ROC curve of WBC count was no statistically significant. When the cut off points of each predictors were evaluated, the higher sensitive was CRP and reached at 90.27% and the higher specific was ESR and reached at 88.50%.
CONCLUSIONFor the patients with fever at the early stage after the PLIF should be paid attention and reasonable choosing predictors are helpful to identify postoperative infection in the early stage. The CRP and ESR may be influenced by the surgery, and the PCT level is helpful to differentiate infection type.
Adult ; Aged ; Aged, 80 and over ; Blood Sedimentation ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Female ; Fever ; blood ; diagnosis ; Fracture Fixation, Internal ; adverse effects ; Humans ; Infection ; blood ; diagnosis ; Leukocyte Count ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Postoperative Complications ; blood ; diagnosis ; Protein Precursors ; blood
9.Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma.
Seung Up KIM ; Jeon Han PARK ; Hyon Suk KIM ; Jae Myun LEE ; Hyun Gyu LEE ; Hyemi KIM ; Sung Hoon CHOI ; Shinhwa BAEK ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Jong Doo LEE ; Kwang Hyub HAN
Yonsei Medical Journal 2015;56(5):1296-1306
PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
Area Under Curve
;
Biomarkers/blood/metabolism
;
Biomarkers, Tumor/blood
;
Carcinoma, Hepatocellular/blood/*diagnosis
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Humans
;
Intercellular Signaling Peptides and Proteins/*blood/*metabolism
;
Liver Neoplasms/blood/*diagnosis
;
Male
;
Middle Aged
;
Protein Precursors/blood/metabolism
;
Prothrombin/metabolism
;
ROC Curve
;
Reverse Transcriptase Polymerase Chain Reaction/*methods
;
Sensitivity and Specificity
;
alpha-Fetoproteins/analysis/metabolism
10.The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma.
Keunhee KANG ; Ji Hoon KIM ; Seong Hee KANG ; Beom Jae LEE ; Yeon Seok SEO ; Hyung Joon YIM ; Jong Eun YEON ; Jong Jae PARK ; Jae Seon KIM ; Young Tae BAK ; Kwan Soo BYUN
Gut and Liver 2015;9(2):224-230
BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.
Adult
;
Age Distribution
;
Aged
;
Anti-Bacterial Agents/therapeutic use
;
Aspartate Aminotransferases/blood
;
Biomarkers/*blood
;
Carcinoma, Hepatocellular/blood
;
Diagnosis, Differential
;
Female
;
Humans
;
Liver Cirrhosis/blood
;
Liver Diseases, Alcoholic/*blood
;
Liver Neoplasms/blood
;
Male
;
Matched-Pair Analysis
;
Middle Aged
;
Multivariate Analysis
;
Protein Precursors/*blood
;
Prothrombin/analysis
;
Retrospective Studies
;
Sex Distribution
;
gamma-Glutamyltransferase/blood

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